Synovial joints, such as the knee, are joints of the body where two adjacent bones are coupled and encapsulated within a synovial membrane or capsule. Ligaments connect bones together while tendons connect bone to muscle. Some joints have cartilage between two or more bones. A synovial membrane substantially surrounds the joint and encapsulates the synovial fluid that fills the joint, thereby forming the joint capsule. The synovial fluid functions to both lubricate and nourish the joint. A synovial joint functions to facilitate full range of normal articulation and movement of the joint that is unique to each patient. As such, maintaining the integrity of the joint allows performance of the patient's day-to-day activities.
There are numerous traumas and/or acute or chronic disorders, which affect the normal workings of a synovial joint and require therapeutic intervention. Examples of joint disorders include, but are not limited to, osteoarthritis, chondromalacia and rheumatoid arthritis, carpal tunnel syndrome, tarsal tunnel syndrome or the like. Additionally, the joint could simply be infected from a post-surgical or prior joint injury. In each of these disorders and traumas the joint is mechanically compromised, either acutely or chronically, causing the body to elicit an immune response. Such a response typically manifests itself as inflammation and/or persistent pain in the joint area.
An example of a joint is a knee joint which contains the tibia and the fibula extending up from the lower leg, the femur extending down from the thigh and the patella as the knee cap over the joint. The medial collateral ligament and the lateral collateral ligament connect the femur to the tibia and fibula, respectively, and restrict the sideways motion of the joint. The posterior cruciate ligament connects the femur to the tibia and restricts backward movement of the joint away from the patella. The anterior cruciate ligament connects the femur to the tibia and restricts the joint rotation and forward motion toward the patella. Examples of traumas to the knee joint include, but are not limited to, tearing and/or fracturing of the anterior cruciate ligament, posterior cruciate ligament, the medial collateral ligament, the lateral collateral ligament, the patellar ligament, the medial meniscus, the lateral meniscus and chondrol fractures.
Inflammation can be an acute response to trauma or a chronic response to the presence of inflammatory agents brought about by any number of processes or events which trigger tissue damage within the synovial joint. For example, when tissues are damaged, tumor necrosis factor-alpha (hereinafter “TNF-α”) attaches to cells causing them to release other cytokines leading to an increase in inflammation. One type of recruited immune system cell is the macrophage. Macrophages release interleukin-1 beta (“IL-1β”) and tumor necrosis factor-alpha (“TNF-α”), pro-inflammatory cytokines heavily involved in orchestrating the immediate and local physiological effects of injury or infection. For instance, once released, pro-inflammatory cytokines promote inflammation. The purpose of the inflammatory cascade is to promote healing of the damaged tissue. However, once the tissue is healed, the inflammatory process does not necessarily end. Left unchecked, the inflammatory process can lead to degradation of surrounding tissues and associated chronic pain. Thus, pain can become a disease state in itself. That is, when this pathway is activated, inflammation and pain ensue. Cycles of inflammation and associated pain often occur long after the initial trauma has or should have resolved.
Current treatment methods of inflammation of the joints include the use of pharmaceutical agents, which are designed to reduce inflammation such that the pain associated with the inflammation subsides and the subject regains at least partial use of the joint. Such pharmaceutical agents include, but are not limited to, analgesics and anti-inflammatory drugs. These drugs can be administered systemically and/or injected directly into the inflamed joint. However, these types of treatments only reduce inflammation for a limited time span. Thus, they are required to be administered regularly by the subject or his/her attending physician.
Recently, however, there have been a number of attempts to develop implants that administer pharmaceutical agents gradually and continuously over a longer time frame. One development has been to use a non-injectable implants such as a depot. A depot is a device that contains and gradually releases a pharmaceutical agent to a targeted region over time. One example of a depot is a capsule that contains the pharmaceutical agent within a biocompatible housing where the end caps of the capsule are comprised of a biodegradable polymer. A second example of a depot is a biodegradable capsule wherein the pharmaceutical agent is distributed homogenously throughout the capsule. With both types of depots, as the biodegradable polymer degrades in the body, the pharmaceutical agent is gradually released.
Some depots can interfere in the movement of the parts of the joints if the depot is placed inside the joint capsule. When that happens, the depot can injure the bone or soft connective tissue within the joint capsule. Instead of alleviating pain and promoting healing, the depot becomes the cause of pain and injury. Thus, there is a need for a depot, which has a shape and is positioned within the joint or next to the joint and can release at least one pharmaceutical agent over a period of time so that the depot allows unfettered movement of the joint while helping the joint heal. In addition, the depot may help prevent or reduce the likelihood of adverse systemic effects of the pharmaceutical agent by having the pharmaceutical agent located at or near the site of injury rather than being administered systemically.